The Mekong Delta in Vietnam is one of the most productive aquaculture regions in the world, in which the red tilapia (Oreochromis spp.) industry is a small-scale industry that mainly supplies local markets in the delta region. Little is known about the frequency of mortality events and health management in this sector. We describe red tilapia floating cage production  systems in the Mekong Delta, Vietnam, for the purposes of quantifying mortality and associated production factors, and describing practices that may influence pathogen introduction and spread to and from farms. In July 2014, approximately 50 red tilapia farmers from 4 provinces (201 farmers in total) were randomly selected and interviewed. Median overall perceived mortality (PM) within a production cycle was 35%. Overall PM was found to be affected by province (p < 0.01), age of farmers (p = 0.01), anticipated main reason for PM in the first 2 wk (p = 0.03), most common market for the fish (p = 0.02), and whether farmers recorded stocking information (p = 0.01). Based on the interviews, we describe and discuss processes that potentially affect pathogen introduction and spread on these farms, such as movements of live and dead fish, distances between farms, mechanical transmission, and biosecurity practices such as treating fish before stocking, using  disinfectants, and sharing equipment, and harvesters’ movements. This study provides fundamental understanding of red tilapia aquaculture management in the Mekong Delta, and describes management factors that could become important in the event of disease outbreaks.